I will test the validity of the hypothesis that the clearance of aminopyrine across the gastric mucosa is blood-flow-limited at basal and stimulated conditions and as such is a legitimate reflection of mucosal blood flow. The uptake and t1/2 for removal of 14C-aminopyrine will be compared to 3HOH or 3H butanol. Different dynamics between 14CAP and 3HOH during histamine stimulation will suggest 14CAP clearance is diffusion-limited at higher flow rates. Anesthetized dogs chambered ex vivo gastric flaps will be used in these and all of the following studies. Local gastric mucosal blood flow will be measured by the washout of 133Xe injected submucosally to determine whether the lesions produced by topical aspirin are preceded by local ischemia. The use of submucosal 133Xe washout will be validated with flowmeter and clearance of aminopyrine. Local blood flow changes in pale areas preceding mucosal ulcerations produced by topical 20 mM aspirin have not been previously evaluated. The pH gradient profile through the gastric mucus gel from apical membrane of the surface epithelial cells to bulk luminal fluid will be studied. The bicarbonate rich mucus layer has recently been reconsidered as a major mucosal protective mechanism. Since the magnitude of the bicarbonate response is 5 to 10% of the maximal acid output for a given mucosal surface, neutralizing capacity of this unstirred mucus layer rich in bicarbonate must be studied directly at the level of the apical membrane of the surface epithelial cell. Micro pH electrodes will be placed at several distances from the apical membrane within the mucus under a variety of (H ion) in the bulk luminal fluid. The thickness of the gastric mucus unstirred layer will be measured with a slit lamp and pachometer optical system. Latex beads will be placed in contact with the gastric epithelium. The optical system will allow accuracy to 10 microns in determining the distance these spheres remain from the epithelium. Mucogenic agents will be administered to determine any change in thickness. These data are important for a mathematical model we are constructing regarding neutralization at the level of the surface epithelial cell.